The pathogenesis of autosomal dominant polycystic kidney disease.

Abstract

In individuals with autosomal dominant polycystic kidney disease (ADPKD), renal function deteriorates as the kidneys become replaced by multitudes of fluid-filled cysts. Although the PKD genes were identified a decade ago, the pathway(s) leading from mutation to disease remain the subject of intense investigation. As a result of this work, it has become apparent that the polycystins are multifunctional proteins that, in the broadest sense, appear to be involved in the transduction of a number of environmental cues into appropriate cellular responses. It is likely that the central pathogenetic pathway for cystogenesis stems from de-differentiation of tubular epithelial cells. Available evidence indicates that loss of polycystin activity leads to subtle derangements of cell calcium regulation through several possible pathways. Abnormal cell calcium homeostasis might then lead to altered differentiation in affected cells. The study of the polycystins has revealed some entirely novel insights into fundamental cell biology but these have not yet been satisfactorily integrated into a verified pathogenetic pathway for the development of ADPKD.

• Authors: Michael Sutters
• Journal: Nephron. Experimental nephrology (Nephron Exp Nephrol) Vol. 103 Issue 4 Pg. e149-55 ( 2006) ISSN: 1660-2129 [Electronic] Switzerland
• PMID: 16691033 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
• Copyright: Copyright 2006 S. Karger AG, Basel

Chemical References

• TRPP Cation Channels
• polycystic kidney disease 1 protein
• polycystic kidney disease 2 protein
• Calcium

Topics

• Calcium (metabolism)
• Cilia (physiology)
• DNA Damage
• Humans
• Polycystic Kidney, Autosomal Dominant (genetics, physiopathology)
• Signal Transduction
• TRPP Cation Channels (metabolism)